Abstract

Individual bacterial lineages stably persist for years in the human gut microbiome. However, it is unknown if these lineages adapt during colonization of healthy people. Here, we assess evolution within individual microbiomes by sequencing the genomes of 602 Bacteroides fragilis isolates cultured from 12 healthy subjects. We find that B. fragilis within-subject populations contain significant de novo nucleotide and mobile element diversity, which preserve years of within-person evolutionary history. This evolutionary history contains signatures of within-person adaptation to both subject-specific and common selective forces, including parallel mutations in seventeen genes. These seventeen genes are involved in cell-envelope biosynthesis and polysaccharide utilization, as well as yet under-characterized pathways. Notably, one of these genes has been shown to be critical for B. fragilis colonization in mice, indicating that key genes have not already been optimized for survival in vivo. This surprising lack of optimization, given historical signatures of purifying selection in these genes, suggests that varying selective forces with discordant solutions act upon B. fragilis in vivo. Remarkably, in one subject, two B. fragilis sublineages coexisted at a stable relative frequency over a 1.5-year period despite rapid adaptive dynamics within one of the sublineages. This stable coexistence suggests that competing selective forces can lead to B. fragilis niche-differentiation even within a single person. We conclude that B. fragilis adapts rapidly within the microbiomes of individual healthy people, with implications for microbiome stability and manipulation.